1. Technical Field
The present invention relates to processes for the preparation of 4′-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone and intermediates thereof.
2. Description of the Related Art
Iloperidone is a neuroleptic and 5-hydroxytryptamine 2A antagonist to be used for the treatment of schizophrenia and general psychosis. Iloperidone is available in the market under the brand name FANAPT® in the form of tablets in the dosage strengths 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, or 12 mg. Iloperidone is chemically known as 4′-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone (herein after referred by its generic name Iloperdione) and represented by the structural formula I

U.S. Pat. No. RE39198 E (U.S. Pat. No. 5,364,866) describes piperidinyl-benzisoxazole derivatives, including iloperidone, a pharmaceutical composition, a method of treatment, and a process for the preparation of iloperidone.
The described prior art processes uses expensive and hazardous chemicals rendering the processes expensive and not viable on commercial scale thus prompting a need for an improved process for the preparation of iloperidone and its intermediates, which avoids the use of hazardous and expensive chemicals, the likely formation of process related impurities.
The preparation of intermediate compound of formula II from novel compounds of formula III and V have not been reported in the literature as of now.
The reported prior art processes uses expensive and hazardous chemicals rendering the processes expensive and not viable on commercial scale. Hence there is a need in the art to provide an improved process for the preparation of iloperidone and its intermediates, which avoids the use of hazardous and expensive chemicals, the likely formation of process related impurities resulting in high yields and purities of the final products.
The applicant has now developed a new industrial synthesis which, in reproducible manner and without requiring laborious purification, yields iloperidone having a purity that is compatible with its use as a pharmaceutical active ingredient, starting from a intermediates obtained from simple and cost effective processes.
The processes of present invention are simple, eco-friendly, inexpensive, reproducible, robust and is well suited on an industrial scale.